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Depression & Stress


And How Proper Care and Feeding of the Adrenals Can Restore that Slimming Metabolic Balance

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The following is an excerpt from Cracking the Metabolic Code by James B. Lavalle, R.Ph., C.C.N., N.D. with Stacy Lundin Yale, R.N., B.S.N.; published by Basic Health Publications, North Bergen, New Jersey; 2004. This excerpt is from Chapter 5 entitled “Balancing Your Adrenals”

Stress of any kind requires an adaptive response from the body. This response is directed by the nervous system but played out, primarily, by the adrenals. The best known of these adaptive responses is the fight-or-flight mechanism first identified by Walter Canon, M.D., in 1931.

The fight-or-flight mechanism is an autonomic nervous system response that allows for important physiologic adjustments in the face of danger.

The stress response begins in the hypothalamus, where nerve impulses from the central nervous system communicate environmental changes to the brain. The hypothalamus, in turn, sends a message to the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenals to release epinephrine, norepinephrine, DHEA (the precursor for the production of both male and female hormones [testosterone and estrogen]), and cortisol.

Cortisol, epinephrine, and norepinephrine released from the adrenal glands provide heightened energy endurance, and perception needed during the alarm mode. DHEA balances some of the effects of cortisol, the adrenal’s principal stress hormone.

Norepinephrine and epinephrine are primarily responsible for the physical changes related to acute stress, which are designed to enhance survival in the face of physical danger. Pupil dilation enhances visual perception. An increased heart rate, as well as an increase in the force of contractions and in breathing, supplies the major organs with blood and oxygen. Blood flow to the brain increases and perception is heightened. Constriction of peripheral blood vessels diverts blood flow from “nonvital” organs, including the stomach and digestive tract. Cortisol increases blood sugar levels by converting noncarbohydrate sources of fuel into glucose.

An increased supply of glucose to the central nervous system enhances brain activity. Cellular metabolism and the production of adenosine triphosphate (ATP) are stepped up, increasing the production of energy in all the cells. So, as you can see, stressful events have quite an impact on your body physically.

Stress can occur at all levels of life. There are nutritional, physical, emotional, mental, psychological, and spiritual stress factors. Even exercise is a type of physical stress. Anxiety, fear, depression, perfectionism, grief, and frustration are stressful. Medical conditions such as infection, chronic illness, or surgery cause tremendous metabolic stress.

Change — even seemingly good change like moving into a new home or starting a new job — can be stressful. Environmental and chemical exposure to pesticides, cleaning agents, drugs, and excessive alcohol use can place stress on the body.

Further, the overuse of over-the-counter and prescription stimulants, including the Chinese herb ma huang (Ephedra) and pseudoephedrine (a chemical used in many diet, sinus, and cold pills) can place stress on adrenal function. For example, thermogenic aids, substances that increase metabolism, containing ma huang have become popular weight-loss tools and are relied on heavily by people for an “energy boost.” Unfortunately, without adequate adrenal support, these aids have the opposite effect in the long term. The energy boost they provide today may ultimately exhaust the adrenals, leading to chronic exhaustion years down the road. I have seen this problem caused by the long-term use of stimulants consistently over the last two decades. Other stimulant abuse, such as excessive caffeine intake, can produce similar results.

In 1967, researchers Homes and Rahe were among the first to study the role of stress in health and wellness. You may already have heard of their “Social Readjustment Rating Scale.” It identifies major life events and their impact on health status by assigning a point value to recently experienced life events. The totalled points give a score that indicates the relative risk of becoming ill from stress-related causes.


Over the last few years several books have been published on the effects of elevated cortisol in your body. From Fight Fat Over Forty: The Revolutionary Three-Pronged Approach That Will Break Your Stress-Fat Cycle and Make You Healthy, Fit, and Trim for Life by Pamela Peeke (Penguin, 2001) to The Cortisol Connection: Why Stress Makes You Fat and Ruins Your Health — and What You Can Do About It by Shawn Talbott (Hunter House, 2002), these books are popular and for a good reason. People are recognizing the effects of chronic stress on their health and are looking for answers.

Cortisol is released in response to the secretion of ACTH from the pituitary gland. The anterior pituitary is signaled by the release of corticotropin releasing hormone (CRH) from the hypothalamus in response to changing conditions. Conditions of stress, including illness and injury, stimulate the hypothalamus and the eventual release of cortisol. Cortisol production is also controlled by what is known as a negative feedback system, when blood levels become low (due to normal cycling), the hypothalamus is stimulated to release more CRH.

Cortisol (termed a glucocorticoid) serves two primary functions: energy production and anti-inflammation. It also causes the constriction of blood vessels. These actions are the means by which they help the body to survive. Cortisol has significant effects on glucose metabolism by influencing fat and protein metabolism. Cortisol increases the blood concentration of amino acids by inhibiting protein synthesis and by stimulating the release of proteins from the muscles if necessary. It also increases the release of fatty acids from adipose tissue for use as a fuel source and stimulates the conversion of noncarbohydrates to glucose. All of these actions serve to regulate the concentration of glucose in the blood to ensure a ready source of fuel for the cells under any type of stress.

Glucocorticoids (95 percent of glucocorticoid production is cortisol) also reduce inflammation and allergic response. For instance, certain cells known as mast cells produce a substance called histamine, a compound in the body that causes an inflammation response. (Any allergy sufferer can tell you about the troublesome effects of histamine.) Cortisol inhibits this production. Other effects of cortisol include decreased permeability of the capillaries and decreased activity of white blood cells. These effects are all life-saving if you are in a traumatic accident or undergoing surgery. However, the continued release of cortisol has some major implications on health.

Although we need cortisol to help the body carry on the function of energy production and to control inflammatory responses, when the hormone is chronically elevated under consistent daily pressures (versus occasional stress or an isolated event), it can cause unwanted effects. One of the functions of cortisol is to help the body produce blood sugar from proteins. This causes an increase in blood sugar levels. If the glucose is not needed for some action such as running or for bodily responses to a trauma, for instance, the excess glucose is then used for lipogenesis (fat production). Numerous studies have linked oversecretion of cortisol with obesity and increased storage of abdominal fat.

Yes, it is true that a basic mechanism of weight gain is an imbalance between caloric intake and energy expenditure. But that is not the total story behind why people gain weight and have trouble losing it. Increasing physiologic, biochemical, and genetic evidence suggests that being overweight is a complex disorder of appetite regulation, energy metabolism, and immune-neuroendocrine miscommunication, involving imbalances in the secretion of regulatory hormones, such as in the thyroid, pituitary, and adrenal glands.

Elevated stress hormones contribute to the breakdown of lean muscle tissue, an increase in blood sugar (causing a problem termed “hyperinsulinemia,” which can lead to insulin resistance and diabetes) and an increase in the storage of abdominal fat. The breakdown of muscle tissue that can occur from stress hormones is very detrimental because muscle tissue is metabolically much more active than fat, meaning it burns more calories. The more muscle tissue you have, the higher you metabolic rate will be. When muscle tissue is lost, metabolic rate decreases, and it becomes much harder to lose weight or to maintain weight loss.

The increase in cortisol release from the adrenal glands causes food cravings, especially for high-fat, high-sugar, high-carbohydrate foods such as cookies, candy, chips, and ice cream. Even though these foods act as a temporary mood “boost,” they in turn feed a vicious cycle, causing additional blood sugar problems, leading to swings in energy and blood sugar, which fuels the stress-cortisol release cycle. Eventually by stimulating excess insulin release, the body is driven to become more insulin resistant, and with more insulin resistance, more fat is stored than the body needs. Sixty to seventy percent of American adults are overweight or obese, and stress-driven food cravings play an ever-increasing role in this weight gain. Even if sufficient exercise is in place to compensate for the extra calories, or the stress is reduced, you may still find yourself in a vicious cycle.

As if the loss of muscle tissue and food cravings were not enough to deal with, adrenal exhaustion can lead to subclinical or overt hypothyroidism and yet another factor that can lead to a lowered metabolism and weight gain.

Another unwanted side effect of too much cortisol production is that it retards regeneration of connective tissue, resulting in slow wound healing. As you may recall, cortisol causes the blood vessels to constrict. This is desired effect if there has been blood loss; however, if there has not, the constricted blood vessels can lead to increased blood pressure and increased risk of cardiovascular disease.

So chronic stress can virtually set in motion the chemistry to make you gain weight and continue to pile it on. Over time, in severe cases, you may even begin to have the appearance of a person with Cushing’s syndrome, which includes a rounded “moon” face, puffiness, buffalo hump or rounding of the upper back, and obesity.

Cortisol competes with thyroid hormone for the amino acid tyrosine, which is also involved in thyroid hormone formation. Excessive cortisol production therefore limits the amount of thyroid hormone that can be produced. Diminished thyroid hormone decreases energy and increases body fat. At the same time cortisol production rises, more and more of the body’s store of DHEA is used up to make more cortisol. As DHEA levels decrease, the effects of the changes in sex hormone levels occur, including reduced libido and increased PMS symptoms. Moreover, cortisol also decreases insulin sensitivity of receptor cells, which decreases the glucose uptake by cells and increases blood sugar. This reduces the energy available to cells, forcing the body to break down muscle tissue for glucose.

Cortisol may also alter immune function. This effect comes from the overall suppression of white blood cell activity, thymus gland dysfunction, and a decrease in natural killer (NK) cell activity in the immune system — hence, reduced immune response. This means that the immune cells responsible for patrolling for foreign agents or cancer cells cannot attack as efficiently. This invites significant risks to your future health. Simultaneously, cortisol will overactivate another part of your immune response, increasing tumor necrosis factor (TNF alpha) and interleukin-6 (IL-6), cytokines that can make the body’s defense system become overactive and lead to autoimmune disorders. It is a tedious balance that the immune system relies on, and cortisol wreaks havoc on that balance.

The results of chronic stress include exhaustion, lowered thyroid function, cardiovascular stress, alterations in blood sugar, weight gain, muscle breakdown, altered immune function, and more. If you don’t think the effects of stress are that big of a deal just look at the following list to see just some of the effects of increased release of cortisol in your system:

• Decreases insulin sensitivity of receptor cells due to increased TNF alpha, thereby stimulating excess insulin release, and increases blood sugar (leading to insulin resistance, hyperinsulinemia, and even diabetes).

• Increases cravings of high-caloric, high-fat, high-sugar, high-carbohydrate foods — even salty foods.

• Increases weight gain, contributes to the breakdown of lean muscle tissue, and increases the storage of belly fat (via increased insulin resistance and lowered thyroid function).

• Causes decreased production of the thyroid gland, leading to subclinical or overt hypothyroidism and a lowered metabolism, increased weight gain, and decreased fatty acid utilization.

• Increases cholesterol and triglycerides, which, in turn, increases cardiovascular risks.

• Increases blood pressure; Causes a loss of sex drive.

• Causes sleep disturbances, marked by an inability to “turn off” the day and wake in the middle of the night typically around 2 to 3 a.m. because of alterations in blood sugar and decreases in serotonin and melatonin production.

• Contributes to tension, complacency, depression, and irritability (by depleting the “calming” brain chemical serotonin).

• Causes destruction of neurological and brain tissue.

• Causes loss of memory through shrinkage of the hypothalamus and reduced circulation.

• Depresses the immune system by increasing neuropeptide Y, which tells the body to turn off the natural killer (NK) cells of the immune system and causes thymus gland atrophy and an inability to produce mature T killer cells.

• Increases IL-6 and TNF alpha, messengers that cause a systemic inflammatory response and overactivates the immune system. In addition, this leads to increased free-radical damage and causes a destructive force in the arteries.

• Increases bone loss.

• Increases water retention.

• Increases catecholamine (epinephrine) production.

Everyone adapts to stress differently, and the healthier your adrenal function is the better you will respond to stress. Inherently strong adrenal glands can withstand longer periods of stress without adverse effects. Conversely, if the adrenals are weakened, the effects of stress will appear more acutely and more quickly. Once again, the adrenal glands are an endocrine gland that can basically wear out with overuse. This is what can lead to adrenal exhaustion, which can then lead to a different set of symptoms, such as low blood pressure, hypoglycemia, mental lethargy, muscle weakness, and weight loss.

But how, once we’ve gotten ourselves into the pit of exhaustion known as adrenal “burnout,” can we climb back out? How can we set things right? The rest of this chapter examines the factors influencing the health of the adrenals, as well as ways to strengthen your resistance to stress.


The key factors that most influence the adrenal glands are stress, thyroid function, nutrients, the pancreas, toxicity, and intestinal or bowel terrain. The following section describes the relationship between each of these key factors and the adrenal response to stress. (Ed: Due to space constraints we have only included the diet section.)


Nutrition has a profound impact on all operating systems of the body, and the adrenal glands are no exception. We have seen the role of nutrients in thyroid and pancreatic function. Like these, the adrenals are dependent on certain vital nutrients to maintain healthy output of adrenal hormones and adequate response to stress.

One of the most important nutrients for healthy adrenal function is salt (sodium). Sodium is needed to drive the synthesis of adrenal hormones. While it is well known that unrestricted salt in the diet can lead to water retention, the adoption of low-sodium diets by many people to control water-weight gain can disrupt the normal functioning of the adrenals. You should consider using reasonable amounts (light salting) of sea salt to provide a broad range of minerals and support the synthesis of important adrenal hormones. People who are chronically adrenal exhausted will crave salt, sometimes uncontrollably.

Those experiencing unavoidable stress, whether acute or chronic, should pay particular attention to nutrition. Stressful times often result in the increased use of caffeine, nicotine, alcohol, and prescription drugs. All of these substances can further compound adrenal stress and may deplete nutrients. Aggravating lifestyle factors, such as excess caffeine, alcohol, the excessive use of stimulants, and/or tobacco should all be curtailed. (I know that this is sometimes easier said than done. But you have to try to make the first step.)


Nutritional deficiencies can lead to physical and emotional stress. Conversely, stress can deplete nutrients. Common nutrients depleted by stress are the antioxidant vitamins C and E, the B vitamins, and the minerals selenium, zinc, magnesium, iron, and sulfur. Carbohydrates, fat, and protein metabolism are all increased during acute stress. And essential fatty acids (EFAs), especially omega-3s, can be depleted through the body’s efforts to dampen the inflammation of stress chemistry. Stress activates inflammatory chemistry cascades; omega-3 fatty acids are our natural defense to dampening our inflammatory response.


Vitamin C, or ascorbic acid, is critical for adrenal function. The adrenal glands have a higher content of vitamin C than any other organ. Vitamin C directly supports the adrenal production of stress hormones. Vitamin C is a potent antioxidant, protecting cells from free-radical damage. (Remember, during times of stress, free-radical damage increases.) Vitamin C also improves resistance to infection by mobilizing white blood cells. It may have a cardioprotective benefit by increasing HDL, or “good,” cholesterol and reducing LDL, or “bad” cholesterol, which increases in the presence of cortisol.


The B vitamins are known as the “antistress” vitamins. Of these, the most important may be vitamin B5, or pantothenic acid. Vitamin B5 depletion is associated with stress, nervous irritability, and adrenal exhaustion. Vitamin B5 is involved in the production of adrenal hormones, and B5 deficiency causes a progressive decline in the production of adrenal hormones.

Along with folic acid and niacin, vitamin B5 is necessary for proper adrenal and nervous system function. Niacin can help counteract some of the biochemical effects of stress, including blood sugar fluctuations and digestive irritation. Vitamin B2 (riboflavin) aids in the production of adrenal hormones. Vitamins B1 (thiamine), B6 (pyridoxine), biotin, and B12 (cyanocobalamin) support the nervous system and can have a calming effect during stressful times.

Vitamin B6 is actually a needed cofactor (catalyst) for serotonin metabolism. Inadequate intake of vitamin B6 can lead to the following: Low serotonin levels, which can lead to feelings of anxiousness, carbohydrate cravings, and depression; If serotonin levels go low enough, falling asleep is difficult or impossible because serotonin is needed to make melatonin (a hormone needed for sleep that also functions as an antioxidant in the body.); Low melatonin interferes with the ability to develop a significant REM (deep) sleep pattern at night, which leads to lighter sleep and to being less rested in the morning, which compounds the impact of stress on the body.

All of the B vitamins are water soluble, which means they cannot be stored by the body. They must be replenished regularly by the diet or by nutritional supplements. Now, don’t kid yourself, if your diet is not that great and you are having some of the problems just listed, you may want to consider finding and taking a multiple vitamin that can give you your full spectrum of needed nutrients. Most multivitamins include a full spectrum of the B vitamins.


Calcium and magnesium are important antistress minerals. Magnesium slows the release of epinephrine and norepinephrine from the adrenal medulla, which makes it a critical mineral for balancing the sympathetic (excitory) nervous system response.

Magnesium helps decrease insulin resistance and stabilizes blood sugar, which is important in counteracting the effects of cortisol. Magnesium increases HDL cholesterol concentration of the blood and balances the cellular absorption of calcium.

Symptoms of magnesium deficiency include anxiety, constipation, fatigue, leg cramps, heart palpitations, insomnia, restlessness, nervousness, and muscle weakness. Severe magnesium loss can result in heart arrhythmias or disruptions in the natural rhythm of the heartbeat.

Because statistics show that 75 percent of Americans are low in magnesium or are getting below the recommended dietary allowances (RDA) for magnesium, I counsel almost all of my patients to start with a magnesium supplement especially since the inadequate intakes are happening at the same time that they are having increased needs (under chronic stress).

Zinc, selenium, copper, and manganese are important for the support of enzymes. Zinc alone is involved in hundreds of enzymatic reactions, including those involved in adrenal activity. Zinc is critical for immune function, specifically the production of T cells from the thymus. High levels of cortisol can deplete zinc status. Excess cortisol and ACTH have been linked to thymus atrophy and shrinkage and suppression of T-cell production. Corticosteroid therapy increases the need for zinc supplementation.

Iron deficiency is associated with reduction of T and B cells (lymphocytes that stimulate and produce antibodies). Iron absorption can be depleted by insufficient hydrochloric acid in the stomach, a symptom of chronic stress. Iron depletion can be a result of extreme physical stress such as exercise. But you shouldn’t take iron unless you have a known iron deficiency or unless you are still menstruating.


One of the most frequent tests I perform in my office is a simple test called a blood spot amino acid profile. It’s usually a surprise to patients when I show them just how low they are in essential amino acids. Amino acids are needed to replenish protein catabolism initiated by chronic cortisol elevations and metabolic challenges. Increasing protein intake during stress is important to maintain adequate amino acid availability. Amino acids are used to synthesize hormones and enzymes crucial for their activities. They are the building blocks of literally all your tissues and the cells needed for metabolic processes.

Tyrosine, an amino acid contained in protein-rich foods, is especially important for endocrine function, and is required for synthesis of epinephrine and norepinephrine, thyroid hormones, and cortisol.

Tryptophan, another amino acid, is needed for the production of serotonin. Eating a high-carbohydrate meal leads to increased tryptophan absorption into the brain where it is made into serotonin. However, as we have mentioned, continually eating too many high-carbohydrate meals can lead to chronically high insulin levels. You can enhance tryptophan absorption by alternating meals that include some complex carbohydrates with high-protein meals. You can also take 5-hydroxytryptophan (5-HTP) to stimulate the production of serotonin. It also is a big help to curb your cravings for carbohydrates and sugar. Often I will recommend 50 mg of 5-HTP in the mid-afternoon and early evening with ReloraTM. ReloraTM is a proprietary formula of a patented extract from Magnolia officinalis and a patent-pending extract from Phellodendron amurense, two plant species that have been used in traditional Chinese medicine (TCM) for over 1,500 years. Both supplements help to reduce excessive stress hormone response and to cut carbohydrate-craving behavior.

The craving for carbohydrates feeds into a vicious cycle of insulin resistance, which fuels further cravings. In addition, the craving pattern associated with elevated cortisol levels can also lead to night eating syndrome (NES) where people will consume 50 percent or more of their calories in the evening. In this syndrome, people will have a lack of appetite during the day. This is most likely due to the effect of stress hormones. NES is characterized by an increased appetite at night and rising up from sleep to eat. This is in part due to poor glycemic or blood sugar regulation and to elevations in cortisol.

This excerpt from Cracking The Metabolic Code – 9 Keys to Optimal Health by James B. LaValle, R.Ph., C.C.N., N.D. is reprinted with permission from the publisher, Basic Health Publications, Inc., North Bergen, NJ. The book is available in selected bookstores and health food stores across Canada, or call the toll free number to order by phone: 1-800-575-8890. Price: US$17.95 / CDN$28.95.


Article Tags: nutrition, vitamins & minerals, stress